Proinflammatory role of leptin in experimental colitis in rats benefit of cholecystokinin-B antagonist and β3-agonist

Maryse Barbier, Samir Attoub, Madeleine Joubert, André Bado, Christian Laboisse, Christine Cherbut, Jean Paul Galmiche

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Leptin, a hormone primarily secreted from adipocytes, plays a key role in controlling body weight homeostasis. In vitro studies indicate that it is also implicated in immune responses. Hyperleptinaemia has been reported in acute inflammation, especially during the early stages of intestinal inflammation in rats. The present study investigated the possible role of leptin in the pathogenesis of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Since no specific antagonist of leptin is available, a CCK-B antagonist (YM022) and a β3 agonist (BRL37344) were used in this study to inhibit leptin secretion. Colitis was induced by intracolonic instillation of TNBS in rats. Five TNBS-groups were subcutaneously implanted with micropumps containing : placebo, YM022, BRL37344, BRL37344 and exogenous leptin simultaneously, or leptin alone. At sacrifices, colitis severity was assessed by macroscopic and histological scoring systems and by determination of tissue myeloperoxidase activity. The TNBS-induced hyperleptinaemia was significantly reduced by YM022 and BRL37344 (p<0.05). Inhibition of leptin secretion markedly reduced colonic inflammation, whatever the criteria considered (i.e. macroscopic, histological or biochemical). In contrast, administration of exogenous leptin completely abolished the beneficial effect of leptin-lowering drugs on colitis severity. These results provide the first direct evidence for an important deleterious role of leptin in the pathogenesis of experimental intestinal inflammation and suggest that a pro-inflammatory activity is attributable to leptin in vivo. Further studies are required to determine if these results have clinical significance.

Original languageEnglish
Pages (from-to)567-580
Number of pages14
JournalLife Sciences
Volume69
Issue number5
DOIs
Publication statusPublished - Jun 22 2001
Externally publishedYes

Keywords

  • BRL37344
  • Experimental rat intestinal inflammation
  • Inflammatory bowel disease
  • Leptin
  • YM022

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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